Electrospray ionization has recently emerged as a powerful technique for producing intact ions in vacuo from large and complex species in solution. To an extent greater than has previously been possible with the more familiar "soft" ionization methods, this technique makes the power and elegance of mass spectrometric analysis applicable to the large and fragile polar molecules that play such vital roles in biological systems. The distinguishing features of electrospray spectra for large molecules are coherent sequences of peaks whose component ions are multiply charged, the ions of each peak differing by one charge from those of adjacent neighbors in the sequence. Spectra have been obtained for biopolymers including oligonucleotides and proteins, the latter having molecular weights up to 130,000, with as yet no evidence of an upper limit.

No abstract

We describe two algorithms that extract molecular mass Information from spectra showing sequences of peaks due to Ions with varying numbers of charges. The first, called here the "averaging algorithm", unambiguously assigns charge numbers to the ions associated with the m/z value for each peak In the sequence and then averages the resulting values of M to give a best estimate of the molecular mass. The second, Identified as the "deconvolution algorithm", mathematically transforms a spectrum of several peaks for multiply charged Ions Into one peak corresponding to a singly charged Ion. The procedures can be readily Implemented with a personal computer and are here applied to representative spectra of small proteins generated by electrospray mass spectrometry. These algorithms are now routinely used In our laboratory for the Interpretation of such spectra. They both are fast and convenient, discriminate against background, and take advantage of much of the information contained In a sequence of peaks. Achievable accuracy and sources of error are discussed.

Ions were produced in an electrospray ionization (ESPI) source from solutions of poly(ethy1ene glycol) (PEG) samples with average molecular weights ranging from 200 to 17 500. Mass analysis of these ions provided evidence that up to at least 23 sodium cations could be deposited on the largest oligomers. A simple model based on equating the affinitiy of an ion for an oxygen site to the electrostatic potential energy of the centermost ion indicates that the capacity of these molecules to hold charge has not yet been reached. Even so, the extent of multiple charging that has already been achieved suggests that ESPI can substantially extend the mass range of an analyzer. In the reported experiments a quadrupole analyzer with an upper limit for m / z of 1500 daltons per charge, with good signal/noise but not-so-good resolution, was able to detect PEG ions whose actual masses were in the range from 15 000 to 20000 daltons! IntroductionPoly(ethy1ene glycols) (PEGs) are interesting model species for characterizing ionization methods used in mass spectrometry. They are commercially available with nominal molecular weights from 200 to 17 500 (e.g., Carbowaxes from Union Carbide). The "nominal molecular weight" refers to the most abundant oligomer in a mixture containing a rather broad distribution of sizes. These commercial products are useful for spectrometer calibration because a wide range of masses can be spanned by a small number of samples. Moreover, each prominent peak in a spectrum is separated from its neighbors by the well-defined and convenient interval of 44 daltons corresponding to the mass of the ethylene oxide building block. This interval is larger, and the relative abundance of each mass less disparate, than is the case for isotopic variants of a single large molecule. On the other hand, the interval is not as large as is the case for singly and doubly charged ions of the same parent molecule. When that parent molecule is large, the spectrometer mass scale must be accurately calibrated over a wide range if one is to be sure that two widely separated peaks indeed correspond to singly and doubly charged species. It will emerge, however, that the broad distribution of oligomer sizes in each sample leads to difficulties with overlapping peaks when extensive multiple charging occurs.Mass spectra for PEGs have previously been obtained with several other soft ionization methods including fast atom bombardment (FAB), thermospray (TS), electrohydrodynamic (EH), and field desorption (FD).1-4 We have found reported results indicating up to four charges per molecule with E H but none showing appreciable multiple charging with TS, FAB, or FD, although up to three charges per molecule have occasionally been observed for other species with these methods as well as with secondary ionization mass spectrometry (SIMS), laser desorption (LD), and plasma desorption (PD) ionization methods. Here we present experimental results which show that electrospray ionization (ESPI) can deposit as many as 23 Na+ ions on PEG

BACKGROUNDInjuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined. METHODSWe conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group. RESULTSThe demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P = 0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% CI, 0.83 to 0.99; P = 0.004). The rates of hospitalization or death were similar in the two groups. CONCLUSIONSA multifactorial intervention, administered by nurses, did not result in a significantly lower rate of a first adjudicated serious fall injury than enhanced usual care.